2013 Articles
A Role for NF-κB Activity in Skin Hyperplasia and the Development of Keratoacanthomata in Mice
Background:
Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin.
Methods:
A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice) with increased NF-κB activity.
Results:
The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata.
Conclusion:
Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.
Subjects
Files
- journal.pone.0071887.PDF application/pdf 2.95 MB Download File
Also Published In
- Title
- PLoS ONE
- DOI
- https://doi.org/10.1371/journal.pone.0071887
More About This Work
- Academic Units
- Microbiology and Immunology
- Publisher
- Public Library of Science
- Published Here
- November 28, 2016